Our research deals largely with the processes of hormone biosynthesis in and secretion from the beta and alpha 2 cells of the endocrine pancreas. Faulty regulation of circulating levels of the insulin and glucagon produced by these cells respectively likely results in the primary and many of the secondary manifestations of the disease diabetes mellitus. The investigation of glucagon formation from its larger, biosynthetic precursor will be approached in two ways. Experiments using isolated pancreatic islets and radioactive amino acids will probe the time course and means of control of the conversion of precursor to product. Experiments on the purification of the precursor from whole pancreas will hopefully result in the isolation of amounts of the precursor sufficient for determination of its chemical structure. Investigations on insulin and glucagon secretion from isolated islets will be approached with the selection of both natural and synthetic agents affecting secretion of the hormones. Through the use of radioactive metabolic probes, a variety of processes ultimately involved in the mechanism of hormone secretion will be studied. These processes include cellular recognition of the secretogog, utilization of metabolic energy during the secretion process and modulation of the secretory response by intracellular metabolites.